Ultrasound provides a unique opportunity to deposit energy remotely into inaccessible human tissue for therapeutic purposes. In the past, such approaches have used one of two mechanisms to activate therapeutic interventions. Ultrasonically deposited energy can be manifested through heat for the activation of heat shock proteins (C. Rome, F. Couillaud and C. T. W. Moonen, Spatial and temporal control of expression of therapeutic genes using shock protein promoters. Methods, 2005. 35(2): p. 188-198), or other temperature sensitive therapies. In addition, ultrasound sensitive particles administered through intra-venous or arterial injection can be used through the incorporation of specific pharmaceutical or genetic material into the particle or on particle shell and the remote activation through the use of specially designed single ultrasound pulses (R. Bekeredjian, P. A. Grayburn, and R. V. Shohet, Use of ultrasound contrast agents for gene or drug delivery in cardiovascular medicine, Journal of the American College of Cardiology, 2005. 45(3): p. 329-335).
Typical ultrasound sensitive particles consist of stabilized microbubbles. These microbubbles are usually less than 5 microns in diameter, stabilized with a shell consisting of protein, lipid, and/or polymers, with gaseous interior. These microbubbles possess the ability to interact with the ultrasound field through resonant behavior within the typical diagnostic imaging frequency range. The resonant behavior can be used to drive the bubbles from a resonant regime where the motion of the bubble is stable to a regime where the bubble expands and collapses violently and transiently. In both cases, it has been observed that when the bubbles incorporate genetic and pharmaceutical material on, within or even in close proximity to the bubble, it is possible to deliver the material to the surrounding tissue using ultrasound.
These prior art methods however suffer from the difficulty that it is impossible to control the rate of release of a material carried by the microbubbles and the spatial location of the released material. As an example, it might be required to deliver material A to a particular tissue, and subsequently material B. Such an operation is not possible with the existing technique. Further, when using ultrasound-mediated gene delivery techniques in vivo or in cell culture, in the past it has not always possible to visualize the presence and the execution of specific instruction sets and the specified outcome of this instruction set.